There is a saying that if you sit in a Paris café long enough, eventually you will see the whole world go by. Secretly, I've always felt that statement could just as easily apply to the Café Synapse in the Gonda (Goldschmied) Neurosciences and Genetics Research Center.

The past few months have only strengthened that conviction. The normal traffic of visiting scientists delivering talks in our longstanding Joint Seminars in Neuroscience, co-sponsored by the Semel Institute, and the constant comings and goings of visiting collaborators, lecturers, and students has continued. But recently that normal traffic has been augmented; in the first few months of 2012 we have welcomed numerous guests distinguished by their accomplishments in the neurosciences, hundreds of young students excited to be on the verge of starting on the same path, and one alumnus charting his own parallel course.

Many of the notable guests drawn to the BRI this month were here for the launch of the Integrative Center for Learning and Memory, which held its inaugural symposium on March 5th and 6th. The Center brings together nearly three-dozen BRI members working in learning and memory. It is indicative of the quality and importance of our work in this area that the launch of the UCLA Center should attract two Nobel laureates – Eric Kandel (2000, Physiology or Medicine) and Susumu Tonegawa (1987, Physiology or Medicine) – who both graciously delivered talks.

Dr. Kandel was once the mentor of our own Kelsey Martin, a Professor in the Departments of Psychiatry and Biobehavioral Sciences and Biological Chemistry, who delivered the final lecture of the symposium. A mere three days earlier, she was interviewed for the PBS program "Closer to Truth," as were myself and fellow BRI-member Robert Bilder, a Professor in the Departments of Psychiatry and Biobehavioral Sciences and Psychology.

Media requests are not entirely out of the ordinary for university professors, but this one was special. "Closer to Truth" is the creation of Robert Lawrence Kuhn, an alumnus of the UCLA neuroscience program who has remained a champion of our work. Robert has charted an amazing career for himself as a financial advisor, respected expert on international politics, and writer. He remains drawn to the big questions about the nature of humanity and cosmology that attracted him to UCLA in the first place, and is committed to communicating with the people in the labs that are pursuing them. It was an honor to meet him and to be engaged by his voraciously curious intellect.

Robert's influence in expanding the popular understanding of the neurosciences is no doubt considerable. We are lucky at the BRI to have many students and professors just as committed to outreach. This semester has been particularly notable in that regard: the BRI-sponsored Los Angeles Brain Bee was held at UCLA for the first time, Brain Awareness Week brought nearly 300 high-school students into our labs in March, and the means through which that project was organized – the Project Brainstorm course – was the subject of a journal article in the prestigious Public Library of Science (Biology).

That is a lot of the world to have gone by in just two months. Look out, Paris.

It is safe to say that the average high school student does not know the function of netrin, semaphorin, and plexin in the brain. Nor are there many that could confidently name cataplexy as the condition in which patients suffer attacks of paralysis in response to emotional triggers.

Anvita Mishra is no average student. Her brain-savvy led the Granite Bay High School sophomore to victory at the 2012 Los Angeles Brain Bee held on January 21st. Mishra has ambitions to become a neurologist, and she traveled the seven hours from her home near Sacramento to pit her neuroscience knowledge against sixteen of her high school peers. "I'm really happy to have won, and I'm looking forward to the Nationals," said Anvita. The winner of that competition wins a summer-long internship at a laboratory in one of the National Institutes of Health.

The Los Angeles Brain Bee, established by Amy Sweetman at Los Angeles City College, consists of a written exam, followed by a lab practicum where students have to identify brain structures and their functions while looking at actual human brains. The exams are followed by two rounds of "Jeopardy!"–style questions and a final elimination round.

Mishra was the runner up to last year's winner, Thanh Liem Huynh-Tran, who went on to win the National and International Brain Bees. "Anvita clearly has the ability to go far in this field," said Chris Evans, Director of the Brain Research Institute (BRI) at UCLA and one of the judges for the Brain Bee. The opportunity to encourage students like Mishra to pursue careers in neuroscience is precisely why the BRI has been a co-sponsor of the Brain Bee for the past three years.

"The Los Angeles Brain Bee is a challenging event and the level of competition is very high," says Evans. "The BRI sponsors the event in partnership with the Zilkha Neurogenetic Institute at USC and Los Angeles City College, but it is really the contestants, and the work they put into it, that makes it a success. Anvita and her fellow competitors are on the path to bright futures in neuroscience."

The Los Angeles Brain Bee provided participants with more than the chance to showcase their neuroscience knowledge; the students were also treated to tours of UCLA neuroscience research laboratories. Professor Jack Van Horn hosted a tour of the Laboratory of NeuroImaging (LONI) that included a spectacular video presentation of neuroimaging technologies used to study the living human brain. The video showed how these technologies are applied to study the healthy brain as well as brains experiencing disease or trauma, how computational methods are used to measure and characterize the brain, and how UCLA scientists are building large-scale databases, sharing data with users worldwide, and developing novel mathematical approaches to better understand brain form and function. Elif Sözmen, a M.D./Ph.D. student in the laboratory of Professor Thomas Carmichael, led a tour which explained his studies on neural injury and brain repair after stroke. The competitors learned about techniques that allow scientists to understand how the brain forms new connections in injured areas after stroke, and how new cells are generated that replace those lost in the aftermath of these traumas. Participants also enjoyed a panel discussion featuring Professors Chris Evans, Tom Otis and Alvaro Sagasti, along with graduate students Laurel Joy Gabard-Durnam, Bonnie Goff, and Sarah Madsen. Just prior to the final rounds of competition, Dr. Eric Hickey from the California School of Forensic Studies at Alliant University in Fresno presented a fascinating lecture titled "Neuroscience of Serial Killers and Psychopaths."

It is this breadth of activity that has led Providence High School science department chair Arjun Harjani to encourage his students to participate in the Brain Bee for the past two years. This year, he brought 12 students from the school's Medical Focus Academic Program, which was an excellent turnout considering they had just finished their exams the day before and had little time to prepare.
"I tell them that they are going to be challenged, but competition isn't the only motivation. The Brain Bee is very effective at increasing interest in neuroscience, no matter the contest's outcome. They enjoy it, and they learn a lot. The students get excited, the parents get excited – I get excited," Harjani said.
Guests at the Brain Bee also enjoyed tours of the UCLA campus, discussion panels hosted by UCLA faculty and graduate students from Project Brainstorm, and neuroscience demonstrations by undergraduate students from the UCLA and USC chapters of the Interaxon science and education outreach student group.

A Project Brainstorm volunteer demonstrates the injury that made Phineas Gage neuroscience's most famous case study. Oscar De La Hoya High School students watch.

Every year, Brain Awareness Week (BAW) draws hundreds of K-12 students to UCLA to learn about neuroscience. This year, nearly 300 students from five Los Angeles-area schools visited the Brain Research Institute.

The chief organizer for this year's five-day event was Martina DeSalvo, a graduate student in the Interdepartmental Ph.D. Program for Neuroscience (NSIDP), working in the laboratory of Dr. Kelsey Martin. "In September, I started to organize different aspects of this event, primarily scheduling the various schools," says DeSalvo. This year, the majority of participating schools were high schools, most of which sent seniors to experience BAW activities. Many of the students have already made their decisions about college, and are contemplating their academic future in a serious way.
"A number of students already know where they're going to college, but after they arrive there are a lot of decisions to be made; if they are pursuing a career in science, there are many paths to consider," said DeSalvo. To help address these questions, Brain Awareness Week activities included career panels during which students had the opportunity to speak to neuroscience faculty, as well as undergraduate and graduate students about their career paths and aspirations.

Brain Awareness Week is a major undertaking each year. Visiting students enjoy a morning of demonstrations at stations where they learn about different functions of the brain, examine human and animal brains, perform brain-challenging exercises such as trying to hit a target while wearing perspective-shifting glasses, tour neuroscience labs, and participate in career panels with faculty and students.

"We had approximately 40 graduate student volunteers, about the same number of undergraduates, and more than 12 faculty members who conducted tours of their labs and generally just helped out," said DeSalvo. "Project Brainstorm students, NSIDP graduate and undergraduate students and Interaxon members all contribute.

Convincing people to participate is not a challenge. It's a wonderful opportunity to interact with students of all ages. It is a great challenge to learn to communicate about what you study in terms that K-12 students can understand. I think it's a great skill to have—to be able to bring science to a general audience. But it's also very fun – the demos are great, and I think the UCLA students conducting the demos enjoy them as much as the visiting Brain Awareness Week participants," said DeSalvo.

"It's a good break from lab work, for sure."

The organizers of BAW gratefully acknowledge support for this event from the UCLA Brain Research Institute, the Center for Student Programming, Campus Programs Committee, the Graduate Student Association's Discretionary Funds, and the Biological Sciences Council.

Project Brainstorm: High-ambition program, high-impact journal

Not often does a paper containing the phrase "fun of neuroscience" appear in a high-impact, peer-reviewed, scientific journal, but it will soon. This accomplishment is due to the trailblazing Project Brainstorm team. The UCLA neuroscience course brings college students into local schools to stimulate interest in science by providing hands-on learning experiences that emphasize the function and importance of the brain.

The influential Public Library of Science Biology (PLOS Biology), which normally confines its contents to traditional observational science, has agreed to publish an article on the BRI-Project Brainstorm coordinated neuroscience course. While a graduate student in the Interdepartmental Ph.D. Program for Neuroscience, Rafael Romero-Calderón and fellow graduate student Elizabeth O'Hare developed the neuroscience course, "Project Brainstorm: Neuroscience K-12 Outreach," along with Dr. Joe Watson, BRI Associate Director for Outreach. Through it, undergraduates are trained to teach neuroscience to elementary, middle, and high school students. The undergraduates are required to make classroom visits to K-12 schools, and develop age-appropriate lessons and activities that demonstrate the brain's functions in a simple, easy-to-grasp manner. The course is highly active, and during the past five years over 100 UCLA undergraduate student have been trained and visited more than 60 classrooms in 30 Los Angeles area schools, reaching over 1,900 K-12 students.

According to Romero-Calderón, the idea to write a paper about Project Brainstorm had been developing for a while. "I thought, wouldn't it be nice if anyone in the world who wanted to reach K-12 students to promote science could know how we do this? Let's put together a paper that thoroughly describes what we do, and publish it in a high-profile science journal. L.A. is very diverse, and there are students from a lot of different backgrounds - we've reached every one, in a lot of different schools."
Romero-Calderón, currently a lecturer in the Department of Molecular, Cell and Developmental Biology, says that for the past two years the UCLA students in the Project Brainstorm course have been trying to quantify their effect in the K-12 classrooms, asking students to take a quiz before and after the Brainstorm sessions to measure their level of knowledge and understanding of the information and materials provided. "We need to show that this is a great project, but we need to show that it is an effective project as well. We hope to publish a follow-up paper with empirical data."

Robert Lawrence Kuhn reviews his notes between takes during a taping of "Closer to Truth" in the Gonda (Goldschmied) Neuroscience and Genetics Research Center.

UCLA alumni Robert Lawrence Kuhn has an eclectic curriculum vitae: he trained as a scientist, made his name in business, and is renowned as an expert on Chinese politics. He recently returned to UCLA in yet another guise: television host. Dr. Kuhn is the creator, executive producer and driving force behind "Closer to Truth," a PBS program described as "the definitive series on Cosmos, Consciousness and God, a global journey in search of the vital ideas of existence."

Dr. Kuhn spent all of Saturday, March 3rd, filming interviews with BRI Director Christopher Evans, and BRI members Kelsey Martin and Robert Bilder for upcoming episodes of the show.

While "Closer to Truth" might appear to be an outlier in a career that also included running and then selling one of the largest mergers and acquisition firms in the U.S., the curiosity motivating the program has been a constant in Dr Kuhn's life, and is the same force that brought him to UCLA in the 1960s.

"Since my youth, I have been interested in the brain and neuroscience, and the relationship between science and philosophy. While I was studying medicine at Johns Hopkins, I stumbled across a book about the brain by [former BRI Director] John French and was fascinated that a 'Brain Research Institute' existed."

Kuhn took a leave of absence from Johns Hopkins University School of Medicine and made his way west, eventually pursuing his Ph.D. degree under the mentorship of now-Emeritus Professor of Neurobiology John Schlag. "Science was always something with which to learn, and appreciate the fundamental questions of life – a way of thinking about things. I learned a great deal from Dr. Schlag in terms of methodology of thought. He let me make mistakes in my experiments – he didn't tell me things were impossible. He let me stumble into things myself, strengthening the lessons I learned."
Dr. Kuhn eventually went to MIT's Sloane School of Management, and in the 1980s wrote a number of books on investment and creative business management. Over time he became an expert on China – even writing a biography of China's former President, Jiang Zemin. In fact, the day after his visit to UCLA, Dr. Kuhn was scheduled to provide commentary to the BBC, CNBC and Bloomberg News on the opening of the 2012 session of the National People's Congress in Beijing.

Dr. Kuhn and BRI Member Dr. Robert Bilder chat in front of the cameras during filming of "Closer to Truth."

Kuhn draws a sharp distinction between his financial and political interests – which he calls his avocation - and "Closer to Truth," which he describes as his passion. The BRI has been a part of that passion since the launch of the program in 2003. "The first time we filmed the program, I invited [former BRI Director] Alan Tobin to appear because I wanted to feature brain science. In a way it was going back to my roots," says Kuhn. Since that first filming, BRI members Arne Scheibel and John Mazziotta have also appeared on the program.

In the current format of the program, Dr. Kuhn discusses selected topics in ten-minute segments, exploring them in an in-depth way, as one might in the course of an engaging dinner party conversation. For Dr. Kuhn, his chosen medium of television allows viewers to connect with the big theories in a way that text alone cannot.

"Everyone we talk to has reams of written material to dive into, but we want to show the personality behind the concepts, draw into their inner psyche, and talk about their fundamental ideas."

As a result, "Closer to Truth" is able to reach people who would not normally be expected to subscribe to Nature or Philosophy. "The audience is unpredictable: you'd think the program would attract viewers with Ph.D.s, but that's not true. The audience's education and background are independent of their interests in these questions," says Kuhn.

"My favorite letter was from a grandmother in Bakersfield who never went to college. She has five sons and a husband, and all of them think she's crazy for being interested in these deep questions on brain and mind and cosmology. She said that her interests have always made her feel like she is an outsider, but now she and her 13 year old grandson sit down and watch 'Closer to Truth.' They know they are not alone in thinking these questions are important. That sort of response is very exciting to me."

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Symposium marks launch of Integrative Center for Learning and Memory

Participants in the Integrative Center for Learning and Memory's Inaugural Symposium gather at a reception in the UCLA Faculty Center.

Sheri Mizumori, Psychology Professor and member of the Center for Integrative Neuroscience at the University of Washington, responds to a question from the audience.

The Integrative Center for Learning and Memory (ICLM) was officially launched with an inaugural symposium on March 5th and 6th, 2012. The first of six Integrative Centers of Excellence in Neuroscience, the new ICLM is home to the active learning and memory community within the Brain Research Institute and UCLA's neuroscience faculty.

The ICLM's inaugural symposium was a tremendous success. Interest in the speakers and lecture topics exceeded expectations, with over 500 registrants filling two auditoriums on campus, which were equipped with a live-stream webcast with interactive capabilities to facilitate communication between them. Attendees enjoyed 24 lectures spanning a wide range of specialization; topics ranged from exploring spatial learning using virtual reality simulators, to studying habituation using high-throughput genetic analyses of C. elegans.

Indicative of the importance of the research being conducted in the field at UCLA, the ICLM symposium succeeded in attracting many distinguished scientists from across the globe, including two Nobel Laureates. Susumu Tonegawa, Ph.D., 1987 Nobel Laureate (Physiology or Medicine), from the Massachusetts Institute of Technology and the RIKEN Brain Science Institute, spoke on "Neural Circuit Genetics of Hippocampal Memory." Eric Kandel, M.D., 2000 Nobel Laureate (Physiology or Medicine) of the Kavli Institute for Brain Science at Columbia University delivered a talk entitled "On the Persistence of Memory Storage."

Kelsey Martin poses with her former postdoctoral supervisor, Eric Kandel.

Intimations of the breadth of topics and techniques to be discussed became evident within the first two talks: Dr. Tonegawa spoke on his efforts to understand the genetic underpinnings of neuronal circuits – manipulating genes over specific timeframes and in specific areas of the brain, and then observing the resulting phenotypes in mouse models. Dr. Tonegawa focuses mainly on hippocampal memory. The same brain region was the subject of the subsequent talk by Mayank Mehta, who is a member of both the BRI and ICLM, and a Professor in the Departments of Physics and Astronomy, Neurology, and Neurobiology. The content was notably different: Mehta's presentation included videos of rats navigating "Tron"-like virtual-reality mazes to the accompaniment of a soundtrack of pops that corresponded to the firing of particular neurons. It is through such experiments that Dr. Mehta explores how spatial environments are represented in neural signals – and how the synaptic plasticity of these neurons interacts with neural rhythms in the process of learning and memory.
The complexity of learning and memory was well illustrated later on the first day, when ICLM member Dean Buonomano, a Professor in the Departments of Neurobiology and Psychology started his talk - "Learning Temporal Patterns in In Vitro Cortical Networks" - with a brief burst of Morse Code (an in-joke for fellow speaker György Buzsáki from Rutgers University, who recognized the dots and dashes as representing his surname). The demonstration served to illustrate the importance of temporal perception to our ability to interpret information: detecting tiny temporal variations – such as those distinguishing Morse dots from dashes – is critical for our capacity to execute fundamental tasks, such as understanding language or music. Buonomano has found that there isn't some centralized "internal clock" in the brain. Instead, the ability to distinguish intervals of time is contained within individual neural circuits, which can be observed in the patterns in which they fire during specific tasks.

György Buzsáki of Rutgers University listens to a question from the audience after his talk.

The diversity on display over the two-day symposium was in keeping with the nature of the ICLM itself. The Center's 34 members form a highly collaborative community that seeks to explore questions that are critical to our understanding of how the human brain analyzes, stores and retrieves information. Learning and memory are functions that are central to our identity as human beings. The ICLM's members are elucidating the mechanisms behind these processes, examining molecular, cellular, systemic and cognitive mechanisms to make important advances in our understanding of the fundamentals of learning, but also of cognitive defects, language acquisition, and disorders ranging from schizophrenia to Alzheimer's Disease.

As the website of the ICLM says, "Answers to these questions are not only transforming our vision of self, they are also having a profound impact in nearly every aspect of the human experience."

Susumu Tonegawa in conversation with M.I.T.'s Li Huei Tsai and Alcino Silva, co-Director of the ICLM.

Enormous as the topics may be, the ICLM provides a unified identity for the scientists at UCLA – be they faculty, post-doctoral fellows or graduate students – that are working in the learning and memory field. These researchers, whether working in molecular or cellular biology, using two-photon or confocal microscopy, electrophysiological or behavioral techniques (among the many others used by ICLM members) are afforded a cohesive organizational structure through the ICLM.
For more information on the Integrative Center for Learning and Memory see:www.iclm.ucla.edu.

Congratulations to BRI Members

John Mazziotta, M.D., Ph.D., has been appointed Executive Vice Dean of the David Geffen School of Medicine and Associate Vice Chancellor at UCLA, effective January 1, 2012. Dr. Mazziotta is currently Chair of the Department of Neurology, Director of the UCLA Brain Mapping Center, Associate Director of the Semel Institute for Neuroscience and Human Behavior, and Professor of Neurology, Radiological Sciences and Molecular and Medical Pharmacology.

In announcing the appointment, Dr. Eugene Washington, Dean of the David Geffen School of Medicine, wrote that Dr. Mazziotta's "entire career exemplifies the kind of creativity, initiative, global thinking and leadership our institution will rely upon over the coming years. In his new role, Dr. Mazziotta will collaborate with the Dean in overseeing all activities related to the David Geffen School of Medicine. In particular, he will serve as the point person for advancing the academic missions of research and education. His operational responsibilities will include academic affairs, space, finances, information systems and administration. He will also continue as Chair of the Department of Neurology."

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BRI member, Jin Hyung Lee, Ph.D., was one of six UCLA professors named as a recipient of a 2012 Sloan Research Fellowship from the Alfred P. Sloan Foundation. In a press release the Sloan Foundation said, "Lee is an Assistant Professor of Electrical Engineering at the UCLA Henry Samueli School of Engineering and Applied Science, with joint appointments in Psychiatry and Biobehavioral Sciences and in Radiology. Her research aims to analyze, debug and engineer brain circuits; her specific goals are to understand the brain's connectivity and its function at the systems level and to develop ways to fix the brain to treat various diseases."
"Sloan Research Fellowships are intended to enhance the careers of exceptional young scientists and scholars in chemistry, computer science, economics, mathematics, evolutionary and computational molecular biology, neuroscience, ocean sciences, and physics."

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The American Association for the Advancement of Science (AAAS) has honored BRI Associate Director for Research David Jentsch, Ph.D., and BRI members Edythe London, Ph.D., and Dario Ringach, Ph.D. with the AAAS Scientific Freedom and Responsibility Award during a ceremony on Friday, February 17th, at the organization's annual conference, held this year in Vancouver, Canada. The organization cited the trio's "rare courage, their strong defense of the importance of the use of animals in research, and their refusal to remain silent in the face of intimidation from animal rights extremists." All three have received death threats from extremist groups, yet continue both in their research and in their public advocacy for the responsible use of animal models in medical research.

UCLA Chancellor Gene Block expressed his admiration for the three faculty members and his appreciation of AAAS, the world's largest general scientific society and the publisher of the journal Science. "David Jentsch, Edythe London and Dario Ringach have demonstrated exemplary courage in the face of reprehensible behavior by extremists, who have resorted to criminal acts in an attempt to intimidate our researchers," Block said. "UCLA will not be deterred from our mission as a public university to continue research that can help improve and save lives. We are very proud of David, Edythe and Dario, and their recognition by the American Association for the Advancement of Science is well deserved."

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Francesco Chiappelli, Ph.D., one of seven UCLA scholars, was named a fellow in the American Association for the Advancement of Science. The selection of fellows has been an AAAS tradition since 1874 and its members are chosen for their distinguished efforts to advance science or its applications. According to the AAAS, "Chiappelli, a professor in the School of Dentistry and a member of both UCLA's Brain Research Institute and Jonsson Comprehensive Cancer Center, was honored for distinguished contributions to the field of oral, dental and craniofacial research, particularly for the unique contributions to development of the field of evidence-based dentistry. His research expertise also includes psycho-neuroendocrine-immune interactions."

Neuroscience Quotables

"The study of connectivity is as hot as hot can get."
~ Susan Bookheimer, Joaquin Fuster Professor of Cognitive Neurosciences in the Department of Psychiatry and Biobehavioral Sciences, quoted in a January 24th article in the Wall Street Journal on international brain mapping efforts.

"Sleep deprivation is an area of huge interest because most of us do not get enough sleep."
~ Christopher Colwell, Professor in the Department of Psychiatry and Biobehavioral Sciences, quoted in a February 15th article in ScienceNews Magazine on research indicating that the brain becomes more reactive and agitated when suffering from sleep deprivation.

"We have learned how to behave ourselves in public, so we may not shout out expletives in a radio interview, or we may not accost someone because we don't like them… When you have an injury to the frontal lobe, that's gone."
~ David Hovda, Director of the UCLA Brain Injury Research Center, quoted on March 13th in DiscoveryNews, commenting on reports that the soldier accused of massacring 17 civilians in Afghanistan may have suffered a traumatic brain injury on a previous tour of duty in Iraq.

"Choices we make every day have a major impact on how our brains age. In fact, physical exercise probably has the most compelling evidence that it can lower the risk of Alzheimer's."
~ Gary Small, Parlow-Solomon Professor on Aging in the Department of Psychiatry and Biobehavioral Sciences, quoted in a March 8th story on CNN about the future costs of caring for Alzheimer's patients.

RESEARCH BRIEFS

A bird's song may teach us about human speech disordersBy Stuart Wolpert

Can the song of a small bird provide valuable insights into human stuttering and speech-related disorders and conditions, including autism and stroke? New research by UCLA life scientists and colleagues provides reason for optimism.

The scientists discovered that some 2,000 genes in a region of the male zebra finch's brain known as "Area X" are significantly linked to singing. More than 1,500 genes in this region, a critical part of the bird's song circuitry, are being reported for the first time. Previously, a group of scientists including the UCLA team had identified some 400 genes in Area X. All the genes' levels of expression change when the bird sings.
"We did not know before that all of these genes are regulated by singing," said Stephanie White, a UCLA associate professor of integrative biology and physiology and senior author of the new study. She believes the 2,000 genes — at least some of which she believes are also shared by humans — are likely important for human speech.

The research is published in the online edition of the journal Neuron, a leading neuroscience journal, and will appear in an upcoming print edition.

"A method that (UCLA co-author) Steve Horvath developed lets us see what genes are changing together and, therefore, which genes are linked in a network," White said. "We can see which are the hub genes that are the most connected to other genes, as in a social network — the popular kids. We can also identify the genetic equivalent of the lonely kids. Steve's analysis lets us group the genes together and see who is interacting with whom."

Many more genes are involved in vocalization than scientists had previously known. While language is uniquely human, it has components — such as the ability to create new sounds — that songbirds and other animals share with us. The zebra finch may create new sounds using the same genes as humans, said White, who is also a member of UCLA's Brain Research Institute.

Male zebra finches learn to sing a courtship song between 35 days and 100 days after hatching, at which point they are sexually mature. Area X is located in the male finch's basal ganglia, beneath the brain's cortex. Only males have the full set of circuitry that allows them to mimic sounds. Female zebra finches don't learn the courtship song and don't have a brain region similar to Area X. Humans don't have an Area X either.

"In your brain, I know that the basal ganglia is involved in your speech, but I don't know exactly which cells," White said. "If I knew which cells, I could see what the genes are. We can't do that in humans, but we can in zebra finches — and we have."
Two genes that seem to be especially important are FoxP2, a "master gene" that directs many other genes to turn on and off and which is critical for both human speech and birdsong, and reelin, a gene that is suspected of causing autism susceptibility in humans. Autistic children often have language difficulties. Both reelin and FoxP2 may play a critical role in human speech and speech disorders.

"No one had ever thought that reelin has a role in vocalization," White said. "We have now found that it is likely important for vocal learning."

UCLA life scientists and their colleagues have provided the first evidence of a causal link between traumatic brain injury and an increased susceptibility to post-traumatic stress disorder.

Their new study, published February 15th in the journal Biological Psychology, also suggests that people who suffer even a mild traumatic brain injury are more likely to develop an anxiety disorder and should take precautions to avoid stressful situations for at least some period of time.

The motivation behind the study, which was conducted in rats, was the observed correlation of traumatic brain injury, or TBI, and PTSD, particularly in military veterans returning from service overseas, said Michael Fanselow, a UCLA professor of Psychology and the senior author of the study.

The reasons for this correlation are unknown. It could be simply that the events that cause brain injury are also very frightening and that the link between TBI and PTSD could be merely incidental. Fanselow and his colleagues, however, hypothesized that the two "could be linked in a more mechanistic way."

Using procedures to separate the physical and emotional traumas, the scientists trained the rats using "fear conditioning" techniques two days after they experienced a concussive brain trauma — ensuring the brain injury and the experience of fear occurred on different days.

"We found that the rats with the earlier TBI acquired more fear than control rats (without TBI)," said Fanselow, a member of UCLA's Brain Research Institute. "Something about the brain injury rendered them more susceptible to acquiring an inappropriately strong fear. It was as if the injury primed the brain for learning to be afraid."

To learn why this occurred, the researchers analyzed a small piece of brain tissue, the amygdala, which is the brain's critical hub for fear learning.

"We found that there are significantly more receptors for excitatory neurotransmitters that promote learning," said Maxine Reger, a UCLA graduate student of psychology in Fanselow's laboratory and the lead author of the study.

"This finding suggests that brain injury leaves the amygdala in a more excitable state that readies it for acquiring potent fear," Fanselow said.

Hyperactivity in brain may explain multiple symptoms of depression
By Mark Wheeler

Maps showing the difference in the strength of brain connections between depressed subjects (left) and controls (right). Depressed subjects show much stronger connections, as evidenced by red colors in their maps.

Most of us know what it means when it's said that someone is depressed. But commonly, true clinical depression brings with it a number of other symptoms. These can include anxiety, poor attention and concentration, memory issues, and sleep disturbances.

Traditionally, depression researchers have sought to identify the individual brain areas responsible for causing these symptoms. But the combination of so many symptoms suggested to UCLA researchers that the multiple symptoms of depression may be linked to a malfunction involving brain networks — the connections that link different brain regions.

Now, for the first time, these UCLA researchers have shown that people with depression have increased connections among most brain areas. Indeed, their brains are widely hyperconnected. The report, published this week in the online journal PLoS One, sheds new light on the brain dysfunction that causes depression and its wide array of symptoms.

"The brain must be able to regulate its connections to function properly," said the study's first author, Dr. Andrew Leuchter, a professor of psychiatry at the Semel Institute for Neuroscience and Human Behavior at UCLA. "The brain must be able to first synchronize, and then later desynchronize, different areas in order to react, regulate mood, learn and solve problems."

The depressed brain, Leuchter said, maintains its ability to form functional connections but loses the ability to turn these connections off.

"This inability to control how brain areas work together may help explain some of the symptoms in depression," he said.

Iron is a popular topic in health news. Doctors prescribe it for medical reasons, and it's available over the counter as a dietary supplement. And while it's known that too little iron can result in cognitive problems, it's also known that too much promotes neurodegenerative diseases.

Now, researchers at UCLA have found that in addition to causing cognitive problems, a lack of iron early in life can affect the brain's physical structure as well.

UCLA neurology professor Paul Thompson and his colleagues measured levels of transferrin, a protein that transports iron throughout the body and brain, in adolescents and discovered that these transferrin levels were related to detectable differences in both the brain's macro-structure and micro-structure when the adolescents reached young adulthood.

Iron and the proteins that transport it are critically important for brain function. Iron deficiency is the most common nutritional deficiency worldwide, causing poor cognitive achievement in school-aged children. Yet later in life, iron overload is associated with damage to the brain, and abnormally high iron concentrations have been found in the brains of patients with Alzheimer's, Parkinson's and Huntington's diseases.

"We found that healthy brain wiring in adults depended on having good iron levels in your teenage years," said Thompson, a member of UCLA's Laboratory of Neuro Imaging. "This connection was a lot stronger than we expected, especially as we were looking at people who were young and healthy — none of them would be considered iron-deficient.

"We also found a connection with a gene that explains why this is so. The gene itself seems to affect brain wiring, which was a big surprise," he said.

Millions of people suffer from Parkinson's disease, a disorder of the nervous system that affects movement and worsens over time. As the world's population ages, it's estimated that the number of people with the disease will rise sharply. Yet despite several effective therapies that treat Parkinson's symptoms, nothing slows its progression.

While it's not known what exactly causes the disease, evidence points to one particular culprit: a protein called a-synuclein. The protein, which has been found to be common to all patients with Parkinson's, is thought to be a pathway to the disease when it binds together in "clumps," or aggregates, and becomes toxic, killing the brain's neurons.
Now, scientists at UCLA have found a way to prevent these clumps from forming, prevent their toxicity and even break up existing aggregates.

UCLA professor of neurology Jeff Bronstein and UCLA associate professor of neurology Gal Bitan, along with their colleagues, report the development of a novel compound known as a "molecular tweezer," which in a living animal model blocked a-synuclein aggregates from forming, stopped the aggregates' toxicity and, further, reversed aggregates in the brain that had already formed. And the tweezers accomplished this without interfering with normal brain function.

The research appears in the current online edition of the journal Neurotherapeutics.

Have you ever gone to the movies and forgotten where you parked the car? New UCLA research may one day help you improve your memory.

UCLA neuroscientists have demonstrated that they can strengthen memory in human patients by stimulating a critical junction in the brain. Published in the Feb. 9 edition of the New England Journal of Medicine, the finding could lead to a new method for boosting memory in patients with early Alzheimer's disease.

The UCLA team focused on a brain site called the entorhinal cortex. Considered the doorway to the hippocampus, which helps form and store memories, the entorhinal cortex plays a crucial role in transforming daily experience into lasting memories.

"The entorhinal cortex is the golden gate to the brain's memory mainframe," said senior author Dr. Itzhak Fried, a professor of neurosurgery at the David Geffen School of Medicine at UCLA. "Every visual and sensory experience that we eventually commit to memory funnels through that doorway to the hippocampus. Our brain cells must send signals through this hub in order to form memories that we can later consciously recall."
Fried and his colleagues followed seven epilepsy patients who already had electrodes implanted in their brains to pinpoint the origin of their seizures. The researchers monitored the electrodes to record neuron activity as memories were being formed.
Using a video game featuring a taxi cab, virtual passengers and a cyber-city, the researchers tested whether deep-brain stimulation of the entorhinal cortex or the hippocampus altered recall. Patients played the role of cab drivers who picked up passengers and traveled across town to deliver them to one of six requested shops.

"When we stimulated the nerve fibers in the patients' entorhinal cortex during learning, they later recognized landmarks and navigated the routes more quickly," Fried said. "They even learned to take shortcuts, reflecting improved spatial memory."

"Critically, it was the stimulation at the gateway into the hippocampus — and not the hippocampus itself — that proved effective," he added.

Patricia Dickson, M.D. obtained her M.D. degree from Columbia University College of Physicians and Surgeons in New York. She then completed an internship and residency in pediatrics at Harbor-UCLA Medical Center, followed by a fellowship in the Intercampus Medical Genetics Training Program. Dr. Dickson is currently an Assistant Professor In-Residence in the Department of Pediatrics.

Dr. Dickson's research focuses on "finding treatments for mucopolysaccharidoses (MPS), a group of rare genetic diseases that cause physical and neurological degeneration and early death. Current projects in the laboratory include intrathecal enzyme replacement therapy for mucopolysaccharidosis type I, the immune response to recombinant enzyme, and developing therapy for the brain in mucopolysaccharidosis type III. Our goal is to develop new treatments and better use of existing treatments for the benefit of people living with MPS."

Sotiris Masmanidis received his Ph.D. degree in applied physics from the California Institute of Technology (CalTech) in Pasadena. He served as a Broad Senior Research Fellow in Brain Circuitry at Caltech until joining UCLA in 2012 as an Assistant Professor in the Department of Neurobiology. Dr. Masmanidis is interested in network-scale neural mechanisms of associative reward learning, sensors for very large-scale electrophysiology, and nanotechnology. "I am investigating how the activity of a neuronal ensemble encodes the association of a sensory cue with a rewarding stimulus, which is relevant to understanding various neuropsychiatric disorders such as drug addiction. I address this problem at the level of multiple interconnected anatomical structures and genetically defined neuronal subpopulations throughout the basal ganglia and limbic system. To achieve this goal, my group is combining the expertise of neuroscientists and device engineers to develop and utilize miniaturized instrumentation for large-scale neuronal recordings from deep brain structures. In addition to electrophysiological studies of reward-mediated learning, we intend to address related questions about the modulatory role of dopamine in shaping our associations with environmental stimuli."

Danny J.J. Wang obtained his Ph.D. in biophysics from the Laboratory of Cognitive Brain Imaging at the University of Science & Technology of China (now the Beijing MRI Center for Brain Research, Institute of Biophysics, Chinese Academy of Sciences). He then completed postdoctoral training in MRI biophysics at the University of Pennsylvania, and upon completion was appointed Research Assistant Professor of Radiology and Neurology. Dr. Wang joined UCLA's Ahmanson-Lovelace Brain Mapping Center in 2010 as an Associate Professor of Neurology, and Radiology. "My main interests are technical development and applications of novel quantitative functional MRI methods such as perfusion and resting state fMRI. My current project involves the development of a multi-modality atlas or template of the developing brain based on perfusion MRI, diffusion tensor imaging (DTI) and resting-state fMRI."

The BRI is happy to welcome its newest members.

Tamkin Foundation makes generous donation in memory of its founder

The Brain Research Institute is grateful to the Tamkin Foundation for their generous donation in memory of Dr. Steven Jerome Tamkin.

Dr. Tamkin was an accomplished entrepreneur, investor, and philanthropist. Born in Los Angeles in 1926, Dr. Tamkin was an officer in the Naval Research Laboratories in the U.S. Navy during World War II. Following his service, Dr. Tamkin attended both USC and UCLA, earning his Ph.D. degree in mechanical and chemical engineering.
Dr. Tamkin was a founder of American Medical International, and TGT Petroleum, as well as an investor in business and real-estate.

As a philanthropist, his good deeds were as diversified as his personal successes; he also extensively dedicated his time to good causes. He helped found the "DARE" teen drug abuse prevention program. He was also a strong supporter of the Boy Scouts of America.

Institutions as diverse as the Los Angeles County Museum of Natural History, Cedars Sinai Medical Center, UCI Medical School, the Betty Ford Center, a number of educational and outreach institutions and, of course, the UCLA medical school and hospital have been beneficiaries of the Tamkin Foundation's support, among many others.

It is a great honor to receive a donation in memory of Dr. Tamkin, and the Brain Research Institute extends its heartfelt thanks to the Tamkin family and the Tamkin Foundation for their generosity.

JOINT SEMINARS IN NEUROSCIENCEWINTER QUARTER 2012

Sponsored by The Brain Research Institute,
The Semel Institute for Neuroscience & Human Behavior,
and the David Geffen School of Medicine at UCLA

The Neuroscience Research Building Auditorium (NRB)We begin promptly at 4:00 pm

April 3, 2012 Charles H. (Tom) Sawyer Distinguished Lecture MARGARET M. MCCARTHY, Ph.D. (Host: Art Arnold and the LNE; arnold@ucla.edu)
Department of Pharmacology, School of Medicine, University of Maryland, Baltimore"Surprising Roles for Neuroinflammatory Mediators and Epigenetics in the Establishment and Maintenance of Sex Differences in the Brain"